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Fawzia Bardag-Gorce

Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, USA

Title: Cultured Autologous Oral Mucosa Epithelial Cell Sheet (CAOMECS) For Corneal Epithelial Regeneration

Biography

Biography: Fawzia Bardag-Gorce

Abstract

Statement of the Problem: Corneal limbal stem-cell deficiency (LSCD) caused by ocular trauma or by eye disease leads to impaired corneal epithelial regeneration and conjunctivalization, neovascularization, which often results in significant vision impairment. Patients with bilateral or unilateral LSCD are currently treated with ex vivo cultured allogeneic or autologous transplant of limbal stem cells.  Allogenic grafts requires immunosuppression, and autologous grafts are associated with other risks. 

The purpose of this study is to use a carrier-free cultured autologous oral mucosal epithelial cell sheet (CAOMECS) graft as a therapeutic approach to improve the health and transparency of the corneal epithelium. 

Methodology & Theoretical Orientation: Using a small biopsy from the buccal cheek, epithelial cells were isolated and cultured for two weeks on a temperature responsive surface (CellSeed Inc. Japan). CAOMECS was harvested and grafted onto the cornea of rabbits with experimentally induced LSCD.

 Findings: Both rabbit and human CAOMECS grafts resulted to a multi‑stratified epithelium similar to corneal epithelium with basal cell positive for DeltaNp63 (a marker of progenitor stem cell).  CAOMECS grafts had a healthy extra‑cellular matrix including balanced pro- and anti‑angiogenic factors and upregulated levels of adhesion molecules necessary for the epithelial integrity. CAOMECS grafting onto corneas of rabbits with LSCD successfully re‑epithelized the ocular surface, reduced cornea vascularization and reduced fibrotic tissue re-growth.  We also demonstrated that diseased corneas with LSCD showed little or no staining for adhesion molecules, while CAOMECS-grafted corneas showed normal expression of adhesion molecules and junctional complexes, which is indicative of a non-migratory behavior of cells in CAOMECS. 

Conclusion & Significance: Carrier-free CAOMECS grafting improved the ocular surface in a rabbit model of LSCD.  CAOMECS grafts renewed corneal epithelial cells, including basal cells positive for progenitor stem cells, acted as a barrier to conjunctivalization and neovascularization, and conferred anti-inflammatory as well as anti-fibrotic effects.